Association between Antibiotic Exposure and the Risk of Rash in Children with Infectious Mononucleosis: a Multicenter, Retrospective Cohort Study.

Present evidence suggests that the administration of antibiotics, particularly aminopenicillins, may increase the risk of rash in children with infectious mononucleosis (IM). This retrospective, multicenter cohort study of children with IM was conducted to explore the association between antibiotic exposure in IM children and the risk of rash. A robust error generalized linear regression was performed to address the potential cluster effect, as well as confounding factors such as age and sex. A total of 767 children (aged from 0 to 18 years) with IM from 14 hospitals in Guizhou Province were included in the final analysis. The regression analysis implied that exposure to antibiotics was associated with a significantly increased incidence of overall rash in IM children (adjusted odds ratio [AOR], 1.47; 95% confidence interval [CI], ~1.04 to 2.08; P = 0.029). Of 92 overall rash cases, 43 were probably related to antibiotic exposure: two cases (4.08%) in the amoxicillin-treated group and 41 (8.15%) in the group treated with other antibiotics. Regression analysis indicated that the risk of rash induced by amoxicillin in IM children was similar to that induced by other penicillins (AOR, 1.12; 95% CI, ~0.13 to 9.67), cephalosporins (AOR, 2.45; 95% CI, ~0.43 to 14.02), or macrolides (AOR, 0.91; 95% CI, ~0.15 to 5.43). Antibiotic exposure may be associated with an increased risk of overall rash in IM children, but amoxicillin was not found to be associated with any increased risk of rash during IM compared to other antibiotics. We suggest that clinicians be vigilant against the occurrence of rash in IM children receiving antibiotic therapy, rather than indiscriminately avoiding prescribing amoxicillin.

Psychometric properties of a Mandarin version of the tinnitus questionnaire.

OBJECTIVE: To develop a Mandarin version of the tinnitus questionnaire (MTQ) and determine the reliability and validity, and to assess whether it could be used clinically in the Chinese population. DESIGN: The MTQ, short-form (36) health survey, hospital anxiety and depression scale, Mandarin (Chinese) tinnitus handicap inventory, and visual analogue scale were completed by the participants. STUDY SAMPLE: We included 192 adults seeking treatment for primary or secondary tinnitus. RESULTS: Five factors, namely, emotional distress, auditory perceptual difficulties, cognitive distress, sleep disturbance, and intrusiveness, were extracted from the MTQ. Thirty-seven items were included. The MTQ had high test-retest reliability (Spearman correlation coefficients: 0.87-1.00). The MTQ and its subscales had good internal consistency and reliability (total α = 0.93, subscales α = 0.71-0.86). A single measure of severity can be acquired by summing the five subscale scores. The MTQ was significantly correlated with psychological distress and tinnitus-related handicap. CONCLUSION: Our results demonstrated that the MTQ is a reliable and valid measure of tinnitus-related psychopathological symptoms and could be used clinically to evaluate tinnitus-related psychological problems. Questionnaires designed to explore tinnitus-related depression and other symptoms not covered by the scope of the MTQ are needed.

An umbrella review of the diagnostic value of next-generation sequencing in infectious diseases.

BACKGROUND: An increasing number of systematic reviews (SRs) have evaluated the diagnostic values of next-generation sequencing (NGS) in infectious diseases (IDs). AIM: This umbrella analysis aimed to assess the potential risk of bias in existing SRs and to summarize the published diagnostic values of NGS in different IDs. METHOD: We searched PubMed, Embase, and the Cochrane Library until September 2023 for SRs assessing the diagnostic validity of NGS for IDs. Two investigators independently determined review eligibility, extracted data, and evaluated reporting quality, risk of bias, methodological quality, and evidence certainty in the included SRs. RESULTS: Eleven SRs were analyzed. Most SRs exhibited a moderate level of reporting quality, while a serious risk of bias was observed in all SRs. The diagnostic performance of NGS in detecting pneumocystis pneumonia and periprosthetic/prosthetic joint infection was notably robust, showing excellent sensitivity (pneumocystis pneumonia: 0.96, 95% CI 0.90-0.99, very low certainty; periprosthetic/prosthetic joint infection: 0.93, 95% CI 0.83-0.97, very low certainty) and specificity (pneumocystis pneumonia: 0.96, 95% CI 0.92-0.98, very low certainty; periprosthetic/prosthetic joint infection: 0.95, 95% CI 0.92-0.97, very low certainty). NGS exhibited high specificity for central nervous system infection, bacterial meningoencephalitis, and tuberculous meningitis. The sensitivity to these infectious diseases was moderate. NGS demonstrated moderate sensitivity and specificity for multiple infections and pulmonary infections. CONCLUSION: This umbrella analysis indicates that NGS is a promising technique for diagnosing pneumocystis pneumonia and periprosthetic/prosthetic joint infection with excellent sensitivity and specificity. More high-quality original research and SRs are needed to verify the current findings.

The Efficacy and Safety of Revefenacin for the Treatment of Chronic Obstructive Pulmonary Disease: A Systematic Review.

Background Revefenacin (REV) is a novel once-daily long-acting muscarinic antagonist (LAMA) in the treatment of moderate to very severe chronic obstructive pulmonary disease (COPD). This systematic review incorporating a dose-response meta-analysis aimed to assess the efficacy and safety of REV. Methods PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP database, and Wanfang database were searched from their inception to April 2020. We included randomized controlled trials (RCTs) which evaluated the efficacy and safety of REV in COPD patients. Two reviewers independently performed study screening, data extraction, and risk of bias assessment. Outcomes consisted of the mean change in trough Forced Expiratory Volume in 1 second (FEV1) from baseline, adverse events (AEs), and serious adverse events (SAEs). A dose-response meta-analysis using the robust error meta-regression method was conducted. We used Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. Results Nine RCTs (3,121 participants) were included in this systematic review. The meta-analyses indicated that 175 µg/day REV could significantly improve the trough FEV1 (MD=143.67, 95%CI: 129.67 to 157.68; I2=96%; 809 participants; studies=4; low quality) without increasing the risk of AEs (OR=0.98, 95%CI: 0.81 to 1.18; I2=34%; 2,286 participants; studies=7; low quality) or SAEs (OR=0.89, 95%CI: 0.55 to 1.46; I2=0%; 2,318 participants; studies=7; very low quality) compared to placebo. Furthermore, the effect of REV in increasing trough FEV1 was dose-dependent with an effective threshold of 88 µg/day (R2 = 0.7017). Nevertheless, only very low-quality to low-quality evidence showed that REV at a dose of 175 µg/day was inferior to tiotropium regarding the long-term efficacy, and its safety profile was not superior to tiotropium or ipratropium. Conclusion Current evidence shows that REV is a promising option for the treatment of moderate to very severe COPD. Due to most evidence graded as low quality, further studies are required to compare the efficacy, long-term safety and cost-effectiveness between REV and other LAMAs in different populations. Clinical Trial Registration: [PROSPERO], identifier [CRD42020182793].

Quality Assessment of the Chinese Clinical Trial Protocols Regarding Treatments for Coronavirus Disease 2019.

BACKGROUND: With the global spread of coronavirus disease 2019 (COVID-19), an increasing number of clinical trials are being designed and executed to evaluate the efficacy and safety of various therapies for COVID-19. We conducted this survey to assess the methodological quality of registry protocols on potential treatments for COVID-19. METHODS: Clinical trial protocols were identified on the ClinicalTrials.gov and the Chinese Clinical Trial Registry. Protocols were screened by two investigators independently against pre-defined eligibility criteria. Quality of the included protocols was assessed according to the modified 14-item SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement. RESULTS: We included 82 randomized controlled trial (RCT) protocols investigating treatment modalities for COVID-19. These ongoing trials are being conducted in 16 provinces, autonomous regions, and municipalities of China, and study interventions were either Western medicines (n = 56) or traditional Chinese medicine (n = 26). Findings of our quality assessment indicated that the existing trial protocols could be further improved on several aspects, including selection and definition of outcome measures, descriptions of study interventions and comparators, study subject recruitment time, definition of study inclusion and exclusion criteria, and allocation concealment methods. Descriptions of random sequence generation methodologies were accurate for the majority of included trial protocols (n = 64; 78.05%); however, reporting of allocation concealment remained unclear in 63 (76.83%) protocols. Therefore, the overall risk of selection bias across these RCTs was judged to be unclear. A total of 52 (63.41%) included RCT protocols were open-label trials and are thus associated with a high risk of performance bias and detection bias. CONCLUSION: Quality of currently available RCT protocols on the treatments for COVID-19 could be further improved. For transparency and effective knowledge translation in real-world clinically settings, it is important for trial investigators to standardize baseline treatments for patients with COVID-19 and assess clinically important core outcome measures. Despite eager anticipation from the public on the results of effectiveness trials in COVID-19, robust design, execution, and reporting of these trials should be regarded as high priority.

The Effectiveness of Clinical Pharmacist-Led Consultation in the Treatment of Infectious Diseases: A Prospective, Multicenter, Cohort Study.

BACKGROUND: Antimicrobial resistance (AMR) is a serious global health threat and leads to a huge challenge to infectious diseases (ID) treatment. To tackle AMR, regional 'Antimicrobial Stewardship Programs' (ASP) have been implemented in many countries. Due to insufficient clinical pharmacy resources, a major intervention mode of ASP in China is through clinical pharmacist-led consultation (CPC). The current study aims to prospectively evaluate this intervention and compare the effectiveness of CPC served by ID and non-ID clinical pharmacists. METHODS: We conducted a prospective and multicenter cohort study based on a regional registry database in 17 hospitals in Western China, including consecutive patients with ID between April 2017 and December 2019. Baseline characteristics including sex, age, liver and kidney function, comorbidity, infection severity were prospectively collected and recorded. The main exposure of interest was whether the attending physician adopted recommendations of the clinical pharmacist in the therapeutic scheme. The outcome was the infection effective response, assessed during day 3-7 after completing CPC. Multivariate analyses were performed by generalized linear mixed models. RESULTS: A total of 2,663 ID patients were included in the final analysis according to the predesigned inclusion and exclusion criteria. The number of patients whose treatment followed and did not follow the pharmacists' suggestion was 2,529 and 134, respectively. CPC intervention could improve the ID patient prognosis in the context of other confounders controlled (Adjusted Odds ratio(AOR)=1.838, 95%Confidence Interval(CI)=[1.212, 2.786]), and the effectiveness of CPC served by ID and non-ID clinical pharmacists might be equivalent (AOR=0.958, 95%CI[0.740, 1.240]). Special consultation (AOR=1.832, 95%CI[1.106, 3.035]) and surgical treatment of infectious sites (AOR=1.380, 95%CI[1.039, 1.834]) had positive influences on the patient prognosis, while hypoalbuminemia (AOR=0.694, 95%CI[0.523, 0.921]), liver dysfunction (AOR=0.705, 95%CI[0.559, 0.889]), presence of high-risk factors (AOR=0.775, 95%CI[0.613, 0.980]), and increased infection severity (AOR=0.631, 95%CI[0.529, 0.753])were associated with a decrease in effective response rate, independently. CONCLUSION: This study suggests that CPC is a promising pharmacist-led intervention to improve ID treatment, and it can achieve standardization among clinical pharmacists with different backgrounds by some measures. Policy/decision-makers should promote this intervention mode in developing countries or regions where there is an insufficient number of clinical pharmacists.

Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements.

OBJECTIVES: Despite the publication of hundreds of trials on gout and hyperuricemia, management of these conditions remains suboptimal. We aimed to assess the quality and consistency of guidance documents for gout and hyperuricemia. DESIGN: Systematic review and quality assessment using the appraisal of guidelines for research and evaluation (AGREE) II methodology. DATA SOURCES: PubMed and EMBASE (27 October 2016), two Chinese academic databases, eight guideline databases, and Google and Google scholar (July 2017). ELIGIBILITY CRITERIA: We included the latest version of international and national/regional clinical practice guidelines and consensus statements for diagnosis and/or treatment of hyperuricemia and gout, published in English or Chinese. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened searched items and extracted data. Four reviewers independently scored documents using AGREE II. Recommendations from all documents were tabulated and visualised in a coloured grid. RESULTS: Twenty-four guidance documents (16 clinical practice guidelines and 8 consensus statements) published between 2003 and 2017 were included. Included documents performed well in the domains of scope and purpose (median 85.4%, range 66.7%-100.0%) and clarity of presentation (median 79.2%, range 48.6%-98.6%), but unsatisfactory in applicability (median 10.9%, range 0.0%-66.7%) and editorial independence (median 28.1%, range 0.0%-83.3%). The 2017 British Society of Rheumatology guideline received the highest scores. Recommendations were concordant on the target serum uric acid level for long-term control, on some indications for urate-lowering therapy (ULT), and on the first-line drugs for ULT and for acute attack. Substantially inconsistent recommendations were provided for many items, especially for the timing of initiation of ULT and for treatment for asymptomatic hyperuricemia. CONCLUSIONS: Methodological quality needs improvement in guidance documents on gout and hyperuricemia. Evidence for certain clinical questions is lacking, despite numerous trials in this field. Promoting standard guidance development methods and synthesising high-quality clinical evidence are potential approaches to reduce recommendation inconsistencies. PROSPERO REGISTRATION NUMBER: CRD42016046104.

Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on major adverse cardiovascular events (MACE). METHODS: Our systematic review included randomised controlled trials if they studied PCSK9 inhibitors in patients for primary and/or secondary prevention of cardiovascular diseases or with hypercholesterolaemia/hyperlipidaemia. Dichotomous variables from individual studies were pooled by relative risks (RR) and their 95% CIs using the random-effect model. Risk difference (RD) in the 10-year frame was also estimated using the pooled RR and the estimated baseline risk using the control group. Grading of Recommendation Assessment, Development and Evaluation was used to assess the quality of evidence. RESULTS: We included 54 trials with 97 910 patients in the analysis. Compared with controls, PCSK9 inhibitors significantly reduced the risk of MACE by 16% (RR, 0.84; 95% CI 0.79 to 0.89; RD: 47 fewer per 1000 vs 286 as the baseline risk; 95% CI 32 to 59 fewer), non-fatal myocardial infarction (MI) by 17% (RR, 0.83; 95% CI 0.74 to 0.93; RD, 35 fewer per 1000 vs 207 as the baseline; 95% CI 13 to 53 fewer) and any stroke by 25% (RR, 0.75; 95% CI 0.65 to 0.85; RD, 16 fewer per 1000 vs 61 as the baseline; 95% CI 9 to 21 fewer) with moderate quality evidence. No significant differences were found between PCSK9 inhibitors and control groups in all-cause mortality, cardiovascular death, heart failure or unstable angina with low-quality evidence. CONCLUSIONS: This study demonstrated that PCSK9 inhibitors could significantly reduce the risk of MACE, non-fatal MI and stroke. TRIAL REGISTRATION: PROSPERO; CRD42017073904.

Chloroquine and hydroxychloroquine are associated with reduced cardiovascular risk: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used in patients with rheumatic diseases, but their effects on the cardiovascular system remain unclear. We aimed to assess whether CQ/HCQ could reduce the risk of cardiovascular disease (CVD). MATERIALS AND METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and the ClinicalTrials.gov for studies investigating the association between CQ/HCQ and the risk of CVD from inception to 20 December 2017. We carried out the quality assessment using the Newcastle-Ottawa Quality Assessment Scale (NOS). Random-effects model was used to pool the risk estimates relative ratio (RR), hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) for the outcomes. RESULTS: A total of 19 studies (7 case-control studies, 12 cohort studies, and no clinical trials) involving 19,679 participants were included in the meta-analysis. Pooled results for HRs or RRs showed that CQ/HCQ was associated with a significantly reduced risk of CVD (pooled RR 0.72, 95% CI 0.56-0.94, p=0.013). Results based on ORs showed a similar tendency towards a reduced risk of CVD with CQ/HCQ (pooled OR 0.41, 95% CI 0.25-0.69, p=0.001). CONCLUSION: Our results suggested that CQ/HCQ was associated with a reduced risk of CVD in patients with rheumatic diseases. Randomized trials are needed to confirm the potential of CQ/HCQ in cardiovascular prevention in patients with and without rheumatic diseases.

Diagnosis and treatment for hyperuricaemia and gout: a protocol for a systematic review of clinical practice guidelines and consensus statements.

INTRODUCTION: Gout and hyperuricaemia are major health issues and relevant guidance documents have been released by a variety of national and international organisations. However, these documents contain inconsistent recommendations with unclear quality profiles. We aim to conduct a systematic appraisal of the clinical practice guidelines and consensus statements pertaining to the diagnosis and treatment for hyperuricaemia and gout, and to summarise recommendations. METHODS: We will search PubMed, EMBASE and guideline databases to identify published clinical practice guidelines and consensus statements. We will search Google and Google Scholar for additional potentially eligible documents. The quality of included guidelines and consensus statements will be assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument and be presented as scores. We will also manually extract recommendations for clinical practice from all included documents. ETHICS AND DISSEMINATION: The results of this systematic review will be disseminated through relevant conferences and peer-reviewed journals. PROTOCOL REGISTRATION NUMBER: PROSPERO CRD42016046104.

Exenatide in obese or overweight patients without diabetes: A systematic review and meta-analyses of randomized controlled trials.

BACKGROUND/OBJECTIVES: Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is increasingly used in obese or overweight patients with diabetes. However, its safety profile and effects on weight loss in non-diabetic obese or overweight population remain unclear. We aimed to evaluate efficacy and safety of exenatide in obese or overweight participants without diabetes. METHODS: We searched up to January 2016 in MEDLINE (Ovid SP), EMBASE (Ovid SP), Cochrane Central Register of Controlled Trials (CENTRAL), some Chinese databases and ClinicalTrials.gov for randomized controlled trials (RCTs) investigating exenatide in obese or overweight participants without diabetes. The primary outcomes included body weight and body mass index (BMI). We pooled data to calculate the mean differences (MDs) with their 95% confidence intervals (CIs). We assessed overall evidence quality of BMI reduction and weight loss according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Six randomized controlled trials involving 362 patients were included in the meta- analysis. The follow-up duration ranged from 12 to 24weeks. Compared with control group, a larger body weight loss (MD: -4.47kg; 95% CI: -6.67 to -2.27; P<0.0001), regardless of dosage and population, was achieved by the obese or overweight patients in exenatide group. Exenatide also elicited a greater reduction in BMI (MD: -0.86kg/m(2); 95% CI: -1.39 to -0.33; P=0.001) and waist circumferences (MD: -1.78cm; 95% CI: -3.13 to -0.44; P=0.009) compared with the control. No significant benefits were showed in exenatide group in terms of blood pressure and lipid profiles. Gastrointestinal adverse events were mostly common during the treatment of exenatide. CONCLUSIONS: Exenatide could significantly reduce body weight in obese or overweight participants without diabetes, and might be a safe alternative GLP-1 receptor agonist for weight control in such patients. Larger randomized trials with longer follow-up duration are required to confirm the effectiveness and safety of exenatide.